Adrenaline-induced “oxygen-wastage” and enzyme release from working rat heart. Effects of calcium antagonism, β-blockade, nicotinic acid and coronary artery ligation

• Published in: Journal of molecular and cellular cardiology Vol. 11; no. 10; pp. 1073 - 1094
• Main Authors: Opie, L.H., Thandroyen, F.T., Muller, Cecilia, Bricknell, O.L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.1979
• Subjects: Adenosine Triphosphate - metabolism; Animals; Calcium - pharmacology; Cardiac output; Cardiac Output - drug effects; Coronary Vessels; Efficiency of heart; Epinephrine - pharmacology; Heart - drug effects; Heart failure; Inotropic effect; L-Lactate Dehydrogenase - metabolism; Lactate dehydrogenase; Ligation; Lipolysis; Male; Myocardium - metabolism; Nicotinic Acids - pharmacology; Oxygen Consumption; Oxygen uptake; Power production; Propranolol; Propranolol - pharmacology; Rats; Verapamil; Verapamil - pharmacology; Work of heart; Heart failure; Power production; Lactate dehydrogenase; Verapamil; Efficiency of heart; Cardiac output; Oxygen uptake; Work of heart; Propranolol; Inotropic effect; Lipolysis
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/0022-2828(79)90395-X

Adrenaline in a high dose (10 −6 m) caused the following harmful effects on mechanical and biochemical parameters of the isolated working rat heart: (i) loss of efficiency of mechanical work from 4.48 ± 0.20 to 3.24 ± 0.13 joules per ml O 2 ( P < 0.001), so that much more oxygen was required to do the same amount of work (“oxygen-wastage”); (ii) a decreased cardiac output despite increased power production (from 14.2 ± 0.7 to 18.9 ± 0.8 mW/g, ( P < 0.001); (iii) a marked release of lactate dehydrogenase (value 10 min after adrenaline: 558 ± 113 mU/g/min; vs control: 16 ± 2); and (iv) a decreased myocardial content of ATP. Interventions to counter the deleterious effects of adrenaline were: calcium antagonism, β-blockade, an antilipolytic agent, and a combination of calcium antagonism and an antilipolytic agent. From this, two separate aspects emerged. First, mechanical function as measured by cardiac output and power production was markedly improved by calcium antagonism which completely reversed the impairment of function caused by the high dose of adrenaline. β-blockade had also a less marked protective effect on mechanical function. Secondly, enzyme release was most effectively inhibited by the combination of calcium antagonism and inhibition of lipolysis or by propranolol. The inefficiency of work (“oxygen-wastage”) was β-mediated and Ca 2+-dependent, whereas enzyme release was predominantly Ca 2+-dependent and partially dependent on lipolysis. Hence the effects of β-blockade in inhibition of the adrenaline-provoked enzyme release could be ascribed to a combination of calcium-antagonism and inhibition of lipolysis.